PROJECT SUMMARY/ABSTRACT--PROJECT 1 Depression is the leading cause of mental health-related morbidity worldwide, affecting approximately 300 million people annually. Depression is nearly twice as prevalent among women than men and multiple individual and psychosocial risk factors are associated with risk of depression. Hispanic women in the US have unique risk factors for depression and other mental health disorders relative to non-Hispanic women including overcoming stress associated with acculturation as well as lower awareness and utilization of mental health care services. Traffic-related and ambient air pollutants are potentially modifiable environmental exposures that are known to disproportionately impact health disparity populations and have increasingly been implicated in risk of depression. Pregnancy is a period of dynamic biological and hormonal fluctuations designed to support fetal development that may increase susceptibility to environmental insults and effects on later depression. Despite growing evidence of the impact of prenatal air pollution on depressive symptoms in the first few months postpartum, there have been no studies on whether exposures during this critical period may increase long-term risk of maternal depression. Understanding biological mechanisms that mediate downstream effects of environmental exposures may lead to improved treatment approaches and reductions in morbidity associated with depression. As primary regulators of gene expression, epigenetic mechanisms, such as microRNA (miRNA), may be important mediators of air pollution effects on depression. MiRNA regulate numerous cellular processes, including neuroendocrine and inflammatory pathways important in depression pathophysiology. We will investigate these mechanisms and the following specific aims in 500 women in the first four postpartum years in the MADRES pregnancy cohort?an ongoing cohort of predominantly Hispanic, socioeconomically- disadvantaged women in urban Los Angeles. We will (1) investigate the association of prenatal exposures to traffic-related and regional air pollution with symptoms of maternal depression in the first four years postpartum and examine whether these associations vary by prenatal psychosocial stressors and acculturation factors; (2) evaluate whether there is a sustained response at 2 and 4 years postpartum between prenatal air pollution exposures and neuroendocrine (cortisol, norepinephrine and epinephrine) and pro-inflammatory markers (IL-6 and CRP) known to be associated with depression; and (3) determine the role of neuroendocrine and inflammatory-related miRNA in prenatal air pollution-related associations in maternal depression in the first four years postpartum and test whether they mediate associations between prenatal air pollution and maternal depression as well as examine the functional relevance of these miRNA. Results from this study may improve policy and treatment approaches to reduce the burden of depression among health disparity populations.